In general, the present disclosure relates to methods and systems for studying the release and diffusion behavior of semi-solid dosage products. In particular, this disclosure relates to the use of a barrier membrane in the study of penetration of bioactive agents in diffusion cell testing using biphasic solvent systems as receptor fluids.
Diffusion cell testing is a common method to study diffusion of a pharmaceutically active compound through tissue. The tissue comprises human or animal tissues, such as, e.g., skin, ocular, buccal, lung, or synthetic membranes. A common method to perform diffusion cell testing is by mounting a piece of tissue between two chambers (donor and receptor chamber). The donor chamber is typically dosed with a pharmaceutically active compound or drug. The receptor chamber is filled with solvent systems, referred to as receptor fluids, to solubilize the compound released from the donor chamber and diffused through the tissue. The receptor fluids are in intimate contact with the mounted tissue in order to solubilize the compound released from the donor chamber and diffused through the tissue.
When a synthetic membrane is used in the diffusion cell testing, the testing is commonly referred to as in vitro release testing (IVRT). IVRT is a common method to study release of a pharmaceutically active compound from semi-solid dosage forms (including ointments, creams, lotions, pastes, and other viscous liquids). In an IVRT, the receptor fluid has two functions: one is as a medium to drive release of the pharmaceutically active compound from the semi-solid dosage forms. The other is as a medium to solubilize the released compound to drive continuation of the release process.
Selection of a suitable receptor fluid is one of most important factors in successfully carrying out an IVRT. To select a suitable receptor fluid, solubility of the pharmaceutically active compound in the fluid needs to be tested to determine if the receptor fluid has adequate solubility for the compound. Solubility of a compound may be determined in a homogenous solvent system. Therefore, receptor fluid is commonly a homogenous solvent system. It might be a single solvent or suitable mixture of miscible solvents.
Depending on exact nature of semi-solid dosage forms, they generally have various degrees of viscosity. The selected receptor fluid needs to drive release of the pharmaceutically active compound from the viscous dosage forms. When a semi-solid dosage form contains a pharmaceutically active compound that has very different physical and chemical property from the dosage form base, selection of a suitable receptor fluid becomes extremely challenging. For example, it is very difficult to select a suitable receptor fluid for an ointment dosage form containing a hydrophilic pharmaceutically active compound in a petrolatum base. Due to highly lipophilic nature of petrolatum base, the receptor fluid must possess high lipophilic property to reduce viscosity of the petrolatum base and drive release of the hydrophilic compound from the petrolatum base. The released hydrophilic compound must, in turn, be efficiently solubilized in the receptor fluid to keep the release process continuing. However, a hydrophilic compound generally has low solubility in a receptor fluid with high lipophilic property. Finding a suitable receptor fluid with favorable ratio of hydrophilicity and lipophilicity is a very tedious process. It requires selecting a large number of solvent systems and conducting a large numbers of IVRT experiments to determine if a selected receptor fluid is suitable. Thus, improvements in conducting IVRT are needed.